Search results for "OUTCOME"
showing 10 items of 5148 documents
Dietary Marine ω-3 Fatty Acids and Incident Sight-Threatening Retinopathy in Middle-Aged and Older Individuals With Type 2 Diabetes Prospective Inves…
2016
IMPORTANCE: Diabetic retinopathy (DR) is a devastating complication of individuals with type 2 diabetes mellitus. The retina is rich in long-chain ω−3 polyunsaturated fatty acids (LCω3PUFAs), which are substrate for oxylipins with anti-inflammatory and antiangiogenic properties. Experimental models support dietary LCω3PUFA protection against DR, but clinical data are lacking. OBJECTIVE: To determine whether LCω3PUFA intake relates to a decreased incidence of sight-threatening DR in individuals with type 2 diabetes older than 55 years. DESIGN, SETTING, AND PARTICIPANTS: In late 2015, we conceived a prospective study within the randomized clinical trial Prevención con Dieta Mediterránea (PRED…
Plasma Metabolites From Choline Pathway and Risk of Cardiovascular Disease in the PREDIMED (Prevention With Mediterranean Diet) Study.
2017
Background-The relationship between plasma concentrations of betaine and choline metabolism and major cardiovascular disease (CVD) end points remains unclear. We have evaluated the association between metabolites from the choline pathway and risk of incident CVD and the potential modifying effect of Mediterranean diet interventions. Methods and Results-We designed a case-cohort study nested within the PREDIMED (Prevention With Mediterranean Diet) trial, including 229 incident CVD cases and 751 randomly selected participants at baseline, followed up for 4.8 years. We used liquid chromatography-tandem mass spectrometry to measure, at baseline and at 1 year of follow-up, plasma concentrations …
Uric acid treatment after stroke modulates the Krüppel-like factor 2-VEGF-A axis to protect brain endothelial cell functions: Impact of hypertension
2019
Uric acid (UA) is a promising protective treatment in ischaemic stroke, but the precise molecular targets underlying its in vivo beneficial actions remain unclear. High concentrations of UA inhibit angiogenesis of cultured endothelial cells via Krüppel-like factor 2 (KLF)-induced downregulation of vascular endothelial growth factor (VEGF), a pro-angiogenic mediator that is able to increase blood–brain barrier (BBB) permeability in acute stroke. Here, we investigated whether UA treatment after ischaemic stroke protects brain endothelial cell functions and modulates the KLF2-VEGF-A axis. Transient intraluminal middle cerebral artery (MCA) occlusion/reperfusion was induced in adult male sponta…
Impact of elosulfase alfa in patients with morquio A syndrome who have limited ambulation: An open-label, phase 2 study.
2017
Efficacy and safety of elosulfase alfa enzyme replacement therapy (ERT) were assessed in an open-label, phase 2, multi-national study in Morquio A patients aged ≥5 years unable to walk ≥30 meters in the 6-min walk test. Patients received elosulfase alfa 2.0 mg/kg/week intravenously for 48 weeks. Efficacy measures were functional dexterity, pinch/grip strength, mobility in a modified timed 25-foot walk, pain, quality of life, respiratory function, and urine keratan sulfate (KS). Safety/tolerability was also assessed. Fifteen patients received elosulfase alfa, three patients discontinued ERT due to adverse events (two were grade 3 drug-related adverse events, the other was not drug-related), …
PDXK mutations cause polyneuropathy responsive to pyridoxal 5′‐phosphate supplementation
2019
OBJECTIVE: To identify disease-causing variants in autosomal recessive axonal polyneuropathy with optic atrophy and provide targeted replacement therapy. METHODS: We performed genome-wide sequencing, homozygosity mapping, and segregation analysis for novel disease-causing gene discovery. We used circular dichroism to show secondary structure changes and isothermal titration calorimetry to investigate the impact of variants on adenosine triphosphate (ATP) binding. Pathogenicity was further supported by enzymatic assays and mass spectroscopy on recombinant protein, patient-derived fibroblasts, plasma, and erythrocytes. Response to supplementation was measured with clinical validated rating sc…
Low-dose agalsidase beta treatment in male pediatric patients with Fabry disease: A 5-year randomized controlled trial.
2019
Abstract Background Fabry disease is a rare, X-linked, lifelong progressive lysosomal storage disorder. Severely deficient α-galactosidase A activity in males is associated with the classic phenotype with early-onset, multisystem manifestations evolving to vital organ complications during adulthood. We assessed the ability of 2 low-dose agalsidase beta regimens to lower skin, plasma, and urine globotriaosylceramide (GL-3) levels, and influence clinical manifestations in male pediatric Fabry patients. Methods In this multicenter, open-label, parallel-group, phase 3b study, male patients aged 5–18 years were randomized to receive agalsidase beta at 0.5 mg/kg 2-weekly (n = 16) or 1.0 mg/kg 4-w…
Effect of nutritional supplementations on physical performance and muscle strength parameters in older people: A systematic review and meta-analysis
2019
Malnutrition plays a role in the development of poor physical performance, frailty and sarcopenia. The use of nutritional supplementations for improving physical performance and muscle strength parameters in older people is unclear. We therefore aimed to summarize the effect of nutritional supplementations compared to placebo on physical performance (i.e. tests more investigating physical function, utilising aerobic capacity & muscle power) and muscle strength (i.e. tests depending on muscle power) outcomes in older people in randomized controlled trials (RCTs). A literature search in major databases was undertaken until the 01st September 2018. Eligible studies were RCTs investigating …
A multicentre, phase IIa study of zolbetuximab as a single agent in patients with recurrent or refractory advanced adenocarcinoma of the stomach or l…
2019
Abstract Background Claudin 18.2 (CLDN18.2) is physiologically confined to gastric mucosa tight junctions; however, upon malignant transformation, perturbations in cell polarity lead to CLDN18.2 epitopes being exposed on the cancer cell surface. The first-in-class monoclonal antibody, zolbetuximab (formerly known as IMAB362), binds to CLDN18.2 and can induce immune-mediated lysis of CLDN18.2-positive cells. Patients and methods Patients with advanced gastric, gastro-oesophageal junction (GEJ) or oesophageal adenocarcinomas with moderate-to-strong CLDN18.2 expression in ≥50% of tumour cells received zolbetuximab intravenously every 2 weeks for five planned infusions. At least three patients …
Effects of DBS in parkinsonian patients depend on the structural integrity of frontal cortex
2017
AbstractWhile deep brain stimulation of the subthalamic nucleus (STN-DBS) has evolved to an evidence-based standard treatment for Parkinson’s disease (PD), the targeted cerebral networks are poorly described and no objective predictors for the postoperative clinical response exist. To elucidate the systemic mechanisms of DBS, we analysed cerebral grey matter properties using cortical thickness measurements and addressed the dependence of structural integrity on clinical outcome. Thirty one patients with idiopathic PD without dementia (23 males, age: 63.4 ± 9.3, Hoehn and Yahr: 3.5 ± 0.8) were selected for DBS treatment. The patients underwent whole-brain preoperative T1 MR-Imaging at 3 T. G…